Our objective is to document changes associated with the early stage of osteoarthritis in dogs and to identify factors which modify the disease.
Our aim i s to examine the role of fibronectin in articular cartilage destruction at an early stage of the osteoarthritic process, before changes in joints can be detected by radiographic methods. We can study this aspect of the disease because of the advantages of the canine model, particularly the spontaneity of the disease, its predictability and expression in several joints of disease-prone dogs (hip, shoulder and knee joints), its slow onset, and our capacity to sample cartilage within and surrounding lesions as well as tissue from unaffected joints. The proposed studies would examine the mechanism for the recently observed increased content and synthesis of fibronectin in the abnormal cartilage of osteoarthritic joints. We want to localize the sites of accumulation of fibronectin using immunohistochemical methods at the electronmicroscopic level. We want to substantiate that fibronectin production is a useful and early marker of osteoarthritis and that its presence is consistent with the idea that chondrocytes from osteoarthritic cartilage have a changed phenotype. We wish to isolate chondrocytes from normal and osteoarthritic cartilage and determine in what ways they differ. We would compare the level of mRNA for fibronectin using available cDNA probes. We would also compare the cell size and shape, DNA content, position in the growth cycle, and the presence of fibronectin or its receptors on the cell surface using both established and novel methods of flow cytometry. Another, but related, aim is to ascertain how to manipulate the culture conditions of explants of """"""""normal"""""""" cartilage in vitro in order to induce increased rates of fibronectin production. These proposed experiments taken together are designed to test the hypothesis that increased fibronectin production is a primary event in the pathogenesis and that chondrocytes from osteoarthritic cartilage are """"""""dedifferentiated.""""""""

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
1R01AR035664-01A1
Application #
3157327
Study Section
General Medicine A Subcommittee 2 (GMA)
Project Start
1986-09-01
Project End
1989-08-31
Budget Start
1986-09-01
Budget End
1987-08-31
Support Year
1
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Cornell University
Department
Type
Schools of Veterinary Medicine
DUNS #
City
Ithaca
State
NY
Country
United States
Zip Code
14850
Chalmers, Heather J; Dykes, Nathan L; Lust, George et al. (2006) Assessment of bone mineral density of the femoral head in dogs with early osteoarthritis. Am J Vet Res 67:796-800
Todhunter, Rory J; Casella, George; Bliss, Stuart P et al. (2003) Power of a Labrador Retriever-Greyhound pedigree for linkage analysis of hip dysplasia and osteoarthritis. Am J Vet Res 64:418-24
Burton-Wurster, N; Liu, W; Matthews, G L et al. (2003) TGF beta 1 and biglycan, decorin, and fibromodulin metabolism in canine cartilage. Osteoarthritis Cartilage 11:167-76
Liu, Wenhua; Burton-Wurster, Nancy; Glant, Tibor T et al. (2003) Spontaneous and experimental osteoarthritis in dog: similarities and differences in proteoglycan levels. J Orthop Res 21:730-7
Todhunter, R J; Bliss, S P; Casella, G et al. (2003) Genetic structure of susceptibility traits for hip dysplasia and microsatellite informativeness of an outcrossed canine pedigree. J Hered 94:39-48
Todhunter, Rory J; Grohn, Yjo T; Bliss, Stuart P et al. (2003) Evaluation of multiple radiographic predictors of cartilage lesions in the hip joints of eight-month-old dogs. Am J Vet Res 64:1472-8
Chen, C T; Burton-Wurster, N; Borden, C et al. (2001) Chondrocyte necrosis and apoptosis in impact damaged articular cartilage. J Orthop Res 19:703-11
Levin, A; Burton-Wurster, N; Chen, C T et al. (2001) Intercellular signaling as a cause of cell death in cyclically impacted cartilage explants. Osteoarthritis Cartilage 9:702-11
Burton-Wurster, N; Gendelman, R; Chen, H et al. (1999) The cartilage-specific (V+C)- fibronectin isoform exists primarily in homodimeric and monomeric configurations. Biochem J 341 ( Pt 3):555-61
Farese, J P; Lust, G; Williams, A J et al. (1999) Comparison of measurements of dorsolateral subluxation of the femoral head and maximal passive laxity for evaluation of the coxofemoral joint in dogs. Am J Vet Res 60:1571-6

Showing the most recent 10 out of 41 publications